TY - JOUR
T1 - Recovery of serum testosterone levels is an accurate predictor of survival from COVID-19 in male patients
AU - Toscano-Guerra, Emily
AU - Gallo, Mónica Martínez
AU - Arrese-Muñoz, Iria
AU - Giné, Anna
AU - Díaz-Troyano, Noelia
AU - Gabriel-Medina, Pablo
AU - Riveiro-Barciela, Mar
AU - Labrador-Horrillo, Moisés
AU - Martinez-Valle, Fernando
AU - Montalvá, Adrián Sánchez
AU - Hernández-González, Manuel
AU - Borrell, Ricardo Pujol
AU - Rodríguez-Frias, Francisco
AU - Ferrer, Roser
AU - Thomson, Timothy M.
AU - Paciucci, Rosanna
N1 - Funding Information:
This study was funded by grants from the Ministerio de Ciencia e Innovación (RTI2018-096055-B-I00), Consejo Superior de Investigaciones Científicas’ COVID-19 Research Fund (CSIC-COV19-006, CSIC-COV19-201), Agència de Gestió d’Ajuts Universitaris i de Recerca (2020PANDE00048 and 2017SGR 1411 GRC), and Plan Nacional de I+D (PID-107139RB-C21) and Instituto Nacional de la Salud Carlos III (PI18/00346 and COVID-19_00416).
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Background: SARS-CoV-2 infection portends a broad range of outcomes, from a majority of asymptomatic cases to a lethal disease. Robust correlates of severe COVID-19 include old age, male sex, poverty, and co-morbidities such as obesity, diabetes, and cardiovascular disease. A precise knowledge of the molecular and biological mechanisms that may explain the association of severe disease with male sex is still lacking. Here, we analyzed the relationship of serum testosterone levels and the immune cell skewing with disease severity in male COVID-19 patients. Methods: Biochemical and hematological parameters of admission samples in 497 hospitalized male and female COVID-19 patients, analyzed for associations with outcome and sex. Longitudinal (in-hospital course) analyses of a subcohort of 114 male patients were analyzed for associations with outcome. Longitudinal analyses of immune populations by flow cytometry in 24 male patients were studied for associations with outcome. Results: We have found quantitative differences in biochemical predictors of disease outcome in male vs. female patients. Longitudinal analyses in a subcohort of male COVID-19 patients identified serum testosterone trajectories as the strongest predictor of survival (AUC of ROC = 92.8%, p < 0.0001) in these patients among all biochemical parameters studied, including single-point admission serum testosterone values. In lethal cases, longitudinal determinations of serum luteinizing hormone (LH) and androstenedione levels did not follow physiological feedback patterns. Failure to reinstate physiological testosterone levels was associated with evidence of impaired T helper differentiation and augmented circulating classical monocytes. Conclusions: Recovery or failure to reinstate testosterone levels is strongly associated with survival or death, respectively, from COVID-19 in male patients. Our data suggest an early inhibition of the central LH-androgen biosynthesis axis in a majority of patients, followed by full recovery in survivors or a peripheral failure in lethal cases. These observations are suggestive of a significant role of testosterone status in the immune responses to COVID-19 and warrant future experimental explorations of mechanistic relationships between testosterone status and SARS-CoV-2 infection outcomes, with potential prophylactic or therapeutic implications.
AB - Background: SARS-CoV-2 infection portends a broad range of outcomes, from a majority of asymptomatic cases to a lethal disease. Robust correlates of severe COVID-19 include old age, male sex, poverty, and co-morbidities such as obesity, diabetes, and cardiovascular disease. A precise knowledge of the molecular and biological mechanisms that may explain the association of severe disease with male sex is still lacking. Here, we analyzed the relationship of serum testosterone levels and the immune cell skewing with disease severity in male COVID-19 patients. Methods: Biochemical and hematological parameters of admission samples in 497 hospitalized male and female COVID-19 patients, analyzed for associations with outcome and sex. Longitudinal (in-hospital course) analyses of a subcohort of 114 male patients were analyzed for associations with outcome. Longitudinal analyses of immune populations by flow cytometry in 24 male patients were studied for associations with outcome. Results: We have found quantitative differences in biochemical predictors of disease outcome in male vs. female patients. Longitudinal analyses in a subcohort of male COVID-19 patients identified serum testosterone trajectories as the strongest predictor of survival (AUC of ROC = 92.8%, p < 0.0001) in these patients among all biochemical parameters studied, including single-point admission serum testosterone values. In lethal cases, longitudinal determinations of serum luteinizing hormone (LH) and androstenedione levels did not follow physiological feedback patterns. Failure to reinstate physiological testosterone levels was associated with evidence of impaired T helper differentiation and augmented circulating classical monocytes. Conclusions: Recovery or failure to reinstate testosterone levels is strongly associated with survival or death, respectively, from COVID-19 in male patients. Our data suggest an early inhibition of the central LH-androgen biosynthesis axis in a majority of patients, followed by full recovery in survivors or a peripheral failure in lethal cases. These observations are suggestive of a significant role of testosterone status in the immune responses to COVID-19 and warrant future experimental explorations of mechanistic relationships between testosterone status and SARS-CoV-2 infection outcomes, with potential prophylactic or therapeutic implications.
KW - COVID-19
KW - Immune phenotype
KW - Longitudinal
KW - Survival
KW - Testosterone
UR - http://www.scopus.com/inward/record.url?scp=85127250532&partnerID=8YFLogxK
U2 - 10.1186/s12916-022-02345-w
DO - 10.1186/s12916-022-02345-w
M3 - Article
C2 - 35351135
AN - SCOPUS:85127250532
VL - 20
JO - BMC Medicine
JF - BMC Medicine
SN - 1741-7015
IS - 1
M1 - 129
ER -